Metformin in Non-Alcoholic Fatty Liver Disease

Inclusion Criteria:

• Histologically proven NAFLD less than 18 months prior to inclusion. For those withpure steatosis, ALAT or aspartate aminotransferase (ASAT) must be elevated above theupper limits of normal, and impaired glucose tolerance or diabetes mellitus type 2must be present.

• Body weight within +/- 5 kg compared with the weight at the time of biopsy.

Exclusion Criteria:

• Treatment for more than 1 week with metformin or glitazones the last 6 months beforeinclusion.

• Treatment with insulin.

• Hypersensitivity to metformin.

• Treatment with cimetidine.

• Heart failure requiring pharmacological treatment.

• Coronary heart disease (New York Heart Association [NYHA] class 3 or 4).

• Chronic obstructive lung disease (moderate or severe).

• Breast-feeding or pregnant.

• Metabolic acidosis.

• Renal failure (male [♂]: creatinine > 135 micromol/L, female [♀] > 110 micromol/L).

• Average alcohol consumption > 24 g/day the last year.

• Serum ALAT or serum ASAT > 5 x upper limit of normal (ULN) at screening.

• Cirrhosis.

• Platelets < 100 000.

• Haemochromatosis.

• Alfa-1-antitrypsin-deficiency.

• Wilson's disease.

• Thyroid dysfunction (0.2 mU/L < thyroid stimulating hormone [TSH] < 5.0 mU/L).

• Chronic infection with hepatitis B or C virus or HIV.

• Autoimmune hepatitis (antinuclear antibodies [ANA] > 1/256 or smooth muscle antibodies [SMA] > 1/128).

• Primary biliary cirrhosis (antimitochondrial antibodies [AMA] > 1/64).

• Primary sclerosing cholangitis.

• Previous participation in another clinical trial the last 6 months.

• Legal incapability.